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Figures

GVAX+α–CTLA-4 combination therapy protects against tumor outgrowth through a CD4+ T cell–dependent mechanism. (A) Mice were challenged with 104 B16-BL6 on day 0, and then left untreated or treated with GVAX, α–CTLA-4, or GVAX+α–CTLA-4 on day 3, 6, and 8. Results depict tumor growth curves of individual mice (A) and cumulative survival (B). n = 10–25 mice per group, death events correspond to a tumor volume >350 mm3 or death of the mouse. (C) Mice were challenged with 5 × 104 B16-BL6 on day 0 and were treated as described above. The CD4+Foxp3−/CD4+Foxp3+ ratio in the lymph node and tumor was calculated. n = 8–10 mice per group. **, P < 0.01; ***, P < 0.001. Experiments were repeated three times and pooled.

Tumor-specific T reg cells are rapidly and cell autonomously eliminated from the tumor by α–CTLA-4. (A) Mice were challenged with 1.5 × 105 B16-BL6 on day 0, adoptively transferred with 5 × 104 CD4+CD45.1+ Trp1 T on day 3, and treated with GVAX or GVAX+α–CTLA-4 on day 3, 6, and 8. Some mice received no further treatment or were treated with α–CTLA-4 on day 3–10, or on day 10 alone, and then sacrificed on day 11. Results depict absolute cell numbers and Foxp3 expression by intratumoral CD4+CD45.1+ Trp1 T cells. n = 9–10 mice per group. (B and C) Wild-type and CTLA-4-huTg mice were treated as described in Fig. 2. Results depict absolute cell numbers and Foxp3 expression by intratumoral CD4+CD45.1+ Trp1 (B) and CD4+CD45.1− endogenous polyclonal T cells (C). (D) CTLA-4+/+ and CTLA-4−/− Trp1 T cells were transferred into wild-type mice, and then treated as described in Fig. 2. Results depict absolute cell numbers and Foxp3 expression by intratumoral CD4+CD45.1+ Trp1 T cells. *, P < 0.05; **, P < 0.01; ***, P < 0.001. Experiments were repeated two times and pooled.